Pressure-sensitive adhesive (PSA) compositions are used in the manufacture of pressure-sensitive adhesive tapes. Such tapes generally comprise a backing substrate and a PSA composition.
One field where PSA compositions find wide spread use is the medical segment, e.g., various tapes, bandages and drug delivery devices. In many such applications, such as for example skin plasters, there is direct contact between the PSA composition and the patient's skin. Adhesives for application to the skin are permanently tacky at room temperature, hold the adhered article to the skin with gentle pressure, and should be easily removed without causing pain or depositing adhesive residue.
In medical applications, the requirements imposed on the PSA composition are especially stringent, since it is necessary to avoid skin irritation and allergic reaction. Moreover, such adhesives need to adhere well to human skin during perspiration, when the weather is hot, or in an environment of draining wounds.
The continuous controlled delivery of drugs through the derma, i.e., skin, provides many advantages over other routes of administration. Transdermal drug delivery is a comfortable, convenient, and noninvasive alternative to other means of drug delivery such as by ingesting medication at fixed time intervals orally or by way of subcutaneous injection. Transdermal drug delivery systems not only allow the controlled release of a pharmaceutical product in a sustained release fashion, but reduce side effects such as gastrointestinal irritation, avoid hepatic first-pass inactivation, poor or erratic absorption from the gastrointestinal tract, and inactivation by the gastrointestinal fluids. Transdermal drug delivery also makes possible a high degree of control over blood concentrations of any particular drug. These advantages enhance patient compliance and improve the safety and efficacy of medications.
In transdermal drug delivery systems, drugs are delivered from a patch applied to the skin with a pressure sensitive adhesive. The known advantages of continuous transdermal drug delivery devices has prompted the development of transdermal drug delivery systems for the administration of a variety of drugs.
Acrylate-based PSAs have been broadly used in transdermal drug delivery systems since they are relatively low in cost compared to other PSAs, solubilize many kinds of functional drugs, adhere well to a variety of different surfaces and, if necessary, can be formulated to build adhesion to a surface. The disadvantages of acrylate-based PSAs include poor high temperature performance, poor low temperature performance, inability to adhere to surfaces with low surface energies and the potential to build excessive adhesion to the skin in medical tape applications which can result in painful removal for the user.
Silicone-based adhesives exhibit both good high and low temperature performance, have excellent chemical inertness, electrical insulating properties, biocompatibility, and the ability to adhere to low surface energy substrates. A primary disadvantage of silicone-based PSAs is their high cost compared to other technologies. Other limitations include lower tack and limited adhesion build, when necessary, in comparison to acrylate-based PSAs.
While both silicone adhesives and acrylic adhesives for application to the skin are known and used in the art, there is an ongoing demand and continuing need for improved PSAs that can be used in medical applications, in particular for drug delivery applications. In transdermal drug delivery applications the pharmaceutically active ingredient normally has very low solubility in a silicone PSA matrix whereas the solubility in an acrylic PSA matrix is normally higher. It is sometimes desirable to achieve an intermediate level of solubility in order to optimize the delivery system for a specific application. A simple approach adopted by Noven Pharmaceuticals, Inc. in U.S. Pat. Nos. 5,474,783, 5,656,286, 6,024,976, 6,221,383, 6,235,306, 6,465,004 and 6,638,528 is to prepare a simple blend of silicone and acrylic PSAs. While optimization of drug solubility can be achieved via this approach, such a blend of incompatible polymers is thermodynamically unstable. This can lead to macroscopic phase separation and changes in adhesive properties with time. An attempt to overcome this problem by creating an acrylic grafted silicone PSA was made by Dow Corning Corp. as disclosed in International Publication No. WO 2007/145996 which uses a three step process where the silicone PSA is first prepared by bodying the gum and resin, then this PSA is capped with a free-radically reactive reagent, and finally acrylic monomer is added and then free-radically polymerized in the presence of the capped-PSA. This complex process makes removal of residual monomer more problematic. High levels of acrylic monomer are unacceptable in skin contact applications. In addition, while free-radical grafting of the silicone and acrylic polymers can take place it is relatively uncontrolled. A further disadvantage of this approach is that an external crosslinker and/or high levels of acid comonomer are required in order to achieve high cohesive strength. High cohesion may be necessary in order to overcome the plasticizing effects of certain active ingredients or other excipients such as skin permeation enhancers leading to adhesive cold flow around the edge of the patch and adhesive residue on the skin following removal of the patch. External crosslinkers such as dibenzoyl peroxide, metal acetyl acetonates or orthoalkyl titanates can result in undesirable byproduct formation resulting from their decomposition or from interaction with the drug. High levels of acid also are undesirable due to the potential for interacting with the drug.
A physical blend of silicone and acrylate are known, however such physical blend is thermodynamically unstable and would lead to macroscopic phase separation and changes in the adhesive properties over time. Also, unreacted silicone and acrylic components are not miscible this can also lead to phase separation over time, even if the rest of components are covalently grafted together.
The present invention describes a method for creating novel covalently grafted blends of silicone and acrylic by using pre-polymerized acrylic polymer, but containing reactive groups and combining it with the precursor to a silicone PSA. These reactive groups on the acrylic are preferably grafted to the silicone PSA during its final reaction phase, known as the “bodying” step, whereby reactive groups on the silicone gum and resin are condensed to form covalent bonds. The acrylic's reactive groups are such as to be able to participate in this bodying process while simultaneously self-crosslinking. Thus the acrylic is grafted to the final silicone PSA in a single step via a more controlled reaction; no acrylic monomer need be removed, and high levels of shear can be obtained without external crosslinking agents or high levels of acid comonomer.
The current invention addresses the need in the art for PSAs that exhibit the advantages of both acrylate- and silicone-based adhesive technologies without the disadvantages inherent in the prior art.